Dr. Philipp Berger

Membrane proteins are at the interface between the extracellular space and the cytoplasma of cells. They transmit signals from other cells to the inside enabling cell type specific answers or they transport essential components into the cell. Our group is interested how synthesis, activation, degradation, and recycling of membrane proteins is regulated. We focus on vascular endothelial growth factor receptor-2 (VEGFR-2) and G-protein coupled receptors (GPCRs). We analyze how these proteins are internalized after stimulation and identify the signals which decide if a receptor is recycled or degraded. Monitoring of these processes needs the simultaneous expression of several fluorescently tagged sensors. Therefore, we developed tools for multigene expression in mammalian cells (MultiLabel, MultiPrime). This allows us to express up to five fluorescently tagged proteins from a single plasmid or baculovirus. Pictures of a cell line stably expressing five fluorescently tagged subcellular markers are shown above. In addition, we also develop image analysis tools to quantify vesicular transport (Squassh, Squassh3C, SquasshAnalyst). These tools allow the segmentation of fluorescence images and the quantification of colocalization between different channels. Manual and installation package are available here for download:
SquasshAnalyst manual.
SquasshAnalyst.zip.
toy_example.zip.

Receptor trafficking - Ballmer-Hofer, K., Andersson, A.E., Ratcliffe, L.E., and Berger, P. (2011). Neuropilin-1 promotes VEGFR-2 trafficking through Rab11 vesicles thereby specifying signal output. Blood 118, 816-826.

MultiLabel/ MultiPrime

- Kriz, A., Schmid, K., Baumgartner, N., Ziegler, U., Berger, I., Ballmer-Hofer, K., and Berger, P. (2010). A plasmid-based multigene expression system for mammalian cells. Nat Commun 1, 120.

- Mansouri, M., Bellon-Echeverria, I., Rizk, A., Ehsaei, Z., Cianciolo Cosentino, C., Silva, C.S., Xie, Y., Boyce, F.M., Davis, M.W., Neuhauss, S.C., et al. (2016). Highly efficient baculovirus-mediated multigene delivery in primary cells. Nat Commun 7, 11529.

Squassh, Squassh3C, SquasshAnalyst

- Rizk, A., Paul, G., Incardona, P., Bugarski, M., Mansouri, M., Niemann, A., Ziegler, U., Berger, P., and Sbalzarini, I.F. (2014). Segmentation and quantification of subcellular structures in fluorescence microscopy images using Squassh. Nature protocols 9, 586-596. - Rizk, A., Mansouri, M., Ballmer-Hofer, K., and Berger, P. (2015). Subcellular object quantification with Squassh3C and SquasshAnalyst. BioTechniques 59, 309-312.

2011-2020

• Baculovirus-based genome editing in primary cells Mansouri M, Ehsaei Z, Taylor V, Berger P
  PLASMID 90, 5 (2017).
  DOI: 10.1016/j.plasmid.2017.01.003

• Highly efficient baculovirus-mediated multigene delivery in primary cells Mansouri M, Bellon-Echeverria I, Rizk A, Ehsaei Z, Cianciolo Cosentino C, Silva Catarina S, Xie Y, Boyce Frederick M, Davis MWayne, Neuhauss Stephan CF, Taylor V, Ballmer-Hofer K, Berger I, Berger P
  NATURE COMMUNICATIONS 7, 11529 (2016).
  DOI: 10.1038/ncomms11529

2010-2015

• Subcellular object quantification with Squassh3C and SquasshAnalyst Rizk A, Mansouri M, Ballmer-Hofer K, Berger P
  BIOTECHNIQUES 59, (2015).
  DOI: 10.2144/000114352

• NRP1 Presented in trans to the Endothelium Arrests VEGFR2 Endocytosis, Preventing Angiogenic Signaling and Tumor Initiation Koch S, van Meeteren Laurens A, Morin E, Testini C, Weström S, Björkelund H, Le Jan S, Adler J, Berger P, Claesson-Welsh L
  DEVELOPMENTAL CELL 28, 633 (2014).
  DOI: 10.1016/j.devcel.2014.02.010
• Segmentation and quantification of subcellular structures in fluorescence microscopy images using Squassh Rizk A, Paul G, Incardona P, Bugarski M, Mansouri M, Niemann A, Ziegler U, Berger P, Sbalzarini I
  NATURE PROTOCOLS 9, 586 (2014).
  DOI: 10.1038/nprot.2014.037
• Strategies for multigene expression in eukaryotic cells Mansouri M, Berger P
  PLASMID 75, 12 (2014).
  DOI: 10.1016/j.plasmid.2014.07.001

• Coordination of VEGF receptor trafficking and signaling by coreceptors Nakayama M, Berger P
  EXPERIMENTAL CELL RESEARCH 319, 1340 (2013).
  DOI: 10.1016/j.yexcr.2013.03.008

• Integration of multiple expression cassettes into mammalian genomes in a single step Kriz A, Schmid K, Ballmer K, Berger P
  Protocol Exchange , (2011).
  DOI: 10.1038/protex.2011.249
• Neuropilin-1 promotes VEGFR-2 trafficking through Rab11 vesicles thereby specifying signal output Ballmer-Hofer K, Andersson AE, Ratcliffe LE, Berger P
  BLOOD 118, 816 (2011).
  DOI: 10.1182/blood-2011-01-328773
• The CMT4B disease-causing proteins MTMR2 and MTMR13/SBF2 regulate AKT signalling Berger P, Tersar K, Ballmer-Hofer K, Suter U
  JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 15, 307 (2011).
  DOI: 10.1111/j.1582-4934.2009.00967.x

2006-2010

• A plasmid-based multigene expression system for mammalian cells Kriz A, Schmid K, Baumgartner N, Ziegler U, Berger I, Ballmer-Hofer K, Berger P
  NATURE COMMUNICATIONS 1, 120 (2010).
  DOI: 10.1038/ncomms1120

• Automated unrestricted multigene recombineering for multiprotein complex production Bieniossek C, Nie Y, Frey D, Olieric N, Schaffitzel C, Collinson I, Romier C, Berger P, Richmond T, Steinmetz M, Berger I
  NATURE METHODS 6, 447 (2009).
  DOI: 10.1038/nmeth.1326
• Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal models Leal A, Huehne K, Bauer F, Sticht H, Berger P, Suter U, Morera B, Del Valle G, Lupski James R, Ekici A, Pasutto F, Endele S, Barrantes R, Berghoff C, Berghoff M, Neundörfer B, Heuss D, Dorn T, Young P, Santolin L, Uhlmann T, Meisterernst M, Sereda M, zu Horste G, Nave K, Reis A, Rautenstrauss B
  NEUROGENETICS 10, 275 (2009).
  DOI: 10.1007/s10048-009-0183-3

• Anti-Mullerian-hormone-dependent regulation of the brain serine-protease inhibitor neuroserpin Lebeurrier N, Launay S, Macrez R, Maubert E, Legros H, Leclerc A, Jamin SP, Picard JY, Marret S, Laudenbach V, Berger P, Sonderegger P, Ali C, di Clemente N, Vivien D
  JOURNAL OF CELL SCIENCE 121, 3357 (2008).
  DOI: 10.1242/jcs.031872

• Mtmr13/Sbf2-deficient mice: an animal model for CMT4B2 Tersar K, Boentert M, Berger P, Bonneick S, Wessig C, Toyka KV, Young P, Suter U
  HUMAN MOLECULAR GENETICS 16, 2991 (2007).
  DOI: 10.1093/hmg/ddm257
• Multiprotein Expression Strategy for Structural Biology of Eukaryotic Complexes Fitzgerald Daniel J, Schaffitzel C, Berger P, Wellinger R, Bieniossek C, Richmond Timothy J, Berger I
  STRUCTURE 15, 275 (2007).
  DOI: 10.1016/j.str.2007.01.016

• Multi-level regulation of myotubularin-related protein-2 phosphatase activity by myotubularin-related protein-13/set-binding factor-2 Berger P, Berger I, Schaffitzel C, Tersar K, Volkmer B, Suter U
  HUMAN MOLECULAR GENETICS 15, 569 (2006).
  DOI: 10.1093/hmg/ddi473
• Pathomechanisms of mutant proteins in Charcot-Marie-Tooth disease Niemann A, Berger P, Suter U
  NEUROMOLECULAR MEDICINE 8, 217 (2006).
  DOI: 10.1385/NMM:8:1:217
• Protein complex expression by using multigene baculoviral vectors Fitzgerald D, Berger P, Schaffitzel C, Yamada K, Richmond T, Berger I
  NATURE METHODS 3, 1021 (2006).
  DOI: 10.1038/nmeth983
• Schwann cells and the pathogenesis of inherited motor and sensory neuropathies (Charcot-Marie-Tooth disease) Berger P, Niemann A, Suter U
  GLIA 54, 243 (2006).
  DOI: 10.1002/glia.20386